This review discusses the important components of ADC design in the context of clinical successes and failures, and evaluates mechanisms of intrinsic and acquired resistance and strategies to overcome these barriers.
Abstract
Antibody-drug conjugates (ADCs) have become an increasingly important component of the therapeutic landscape of many solid tumors. Currently, there are eight ADCs approved for solid tumors, with hundreds being developed and in clinical trials. Initially being approved in the advanced or metastatic settings, ADCs are also being incorporated as neoadjuvant or adjuvant therapies. In this review, we discuss the important components of ADC design in the context of clinical successes and failures. We further evaluate mechanisms of intrinsic and acquired resistance and strategies to overcome these barriers. Finally, we discuss the landscape of potential combination partners to increase efficacy of ADC therapies.
This review systematically summarizes the major mechanisms underlying ADC resistance in BC and outlines potential strategies to overcome it, including the development of next-generation ADCs, combination therapies, and predictive biomarkers.
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